Integrative gene expression profiling reveals that dysregulated triple microRNAs confer paclitaxel resistance in non-small cell lung cancer via co-targeting MAPT

作者：Yuanming Cai, Ruxue Jia, Haozhe Xiong, Qun Ren, Weimin Zuo, Tingting Lin, Rong Lin, Lei Yan, Ping Wang, Huiyue Dong, Hu Zhao, Ling Zhu, Yunfeng Fu, Zhiyong Zeng, Wei Zhang, Shuiliang Wang · 发表于：Cancer Management and Research · 年份：2019 · DOI：10.2147/cmar.s215427 · 被引用次数：19 · 研究领域：MicroRNA in disease regulation、Lung Cancer Treatments and Mutations、Flavonoids in Medical Research

BACKGROUND: Paclitaxel has shown significant anti-tumor activity against non-small cell lung cancer (NSCLC); however, resistance to paclitaxel frequently occurs and represents a significant clinical problem and its underlying molecular mechanism remains elusive. METHODS: Long-term treatment of culture cell with paclitaxel was carried out to mimic the development of acquired drug resistance in NSCLC. Cell proliferation and clonogenic assay and apoptosis evaluation were carried out to determine the efficacy of paclitaxel on NSCLC cells. Western blot analyses were performed to determine the expression and activation of proteins. Apoptosis enzyme-linked immunosorbent assay was used to quantify cytoplasmic histone-associated DNA fragments. Microarray analyses were applied to explore both mRNA and miRNA expression profiles in NSCLC cells followed by integrative analysis. qRT-PCR was carried out to verify the differentially expressed mRNAs and miRNAs. RESULTS: The expression of 652 genes was shown to be changed at least 2-fold in paclitaxel-resistant NSCLC (H460_TaxR) cells with 511 upregulated and 141 downregulated as compared with that in parental H460 cells. The differentially expressed genes were functionally enriched in regulating the cell proliferation, cell death, and response to endogenous stimulus, and clustered in pathways such as cancer and signaling by the G protein-coupled receptor (GPCR). Moreover, 43 miRNAs were shown to be differentially expressed in H460_TaxR cells ...